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Rat model of left ventricular remodeling TCM Syndrome evaluation and electrophysiological effects of Chinese medicine

Author: NiLiang
Tutor: WangShuoRen
School: Beijing University of Traditional Chinese Medicine
Course: Within the science of Traditional Chinese Medicine
Keywords: left ventricle remodeling animal model traditional Chinese medicine syndrome Chinese materia medica electrophysiology
CLC: R-332;R259
Type: PhD thesis
Year: 2007
Downloads: 252
Quote: 1
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Abstract


Arrhythmia,which is a serious threat to human health, is a kind of heart disease. Serious arrhythmia has become the leading cause of death. And the long-standing, effective treatment of arrhythmia is the weak links for Chinese medicine and combination of TCM with Western medicine. Therefore this study is to launch prevention and treatment of Arrhythmia Research.Objectives:1. The establishment of coarctation rats abdominal aorta induced animal model of ventricular remodeling, and the research of traditional Chinese medicine syndrome.2. To study electrophysiological characteristics of isolated heart of ventricular remodeling in rats, and to make pharmacological research of application of active Blood and Yiqi medicine extracts to treat arrhythmia, which caused by ventricular remodeling.Methods:1. To duplicate the rat ventricular remodeling in animal models with coarctation rats abdominal aorta. Application of echocardiography technology and pathology laboratory to evaluate the pathologic characteristics of rat hearts right model after four weeks and eight weeks. Based on diagnostic standard of Integrated Traditional Chinese and Western Medicine about deficient syndrome and syndrome of blood stasis, with acquisition of the apparent external information and evaluation of cardiac function, conduct animal disease and syndrome comprehensive evaluation in animal model.2. Application of coronary artery ligation and abdominal aorta coarctation in rats to duplicate two kinds of ventricular remodeling animal model. With the method of Langdorff reperfusion isolated rat cardiac electrophysiology experimental, electrophysiology index, which including 20% action potential duration(APD20,ms), 50% action potential duration(APD50,ms), 90% action potential duration(APD90,ms), effective refractory period(ERP,ms), action potential amplitude(APA,mv), maximum velocity of phase depolarization(Vmax,v/s), APD90 divergence and ERP divergence, at 8 weeks right after operation. To study its electrophysiological characteristics. 3. With the above in vitro perfusion of cardiac electrophysiology experimental, using lidocaine, amiodarone, verapamil as a positive control, make the research about electrophysiology impact of pharmaceutics remedies (gensenosides, trtram-ethylpvrazine, gensenosides and trtram-ethylpvrazine, sophordine, berbeine) on the rat ventricular remodeling in animal models with coarctation rats abdominal aorta.4.With the above in vitro perfusion of cardiac electrophysiology experimental, studying the electrophysiology impact of Fuzhenghuayu caps(0.4g/kg)and captopril(2.2mg/kg) on the rat ventricular remodeling in animal models with coronary artery ligation.Results:1. At 4 weeks of operation, in rat ventricular remodeling in animal models with coarctation rats abdominal aorta, inter-ventricular septum end-diastolic thickness(IVSTd),left ventricular mass index(LVMI),left ventricular wall thickness, left ventricular cavity area, collagen volume fraction (CVF), Perivascular Collagen area (PVCA) and leads of ST-segment changes increased (P <0.01), heart rate increased (P <0.05), exhaustive swim time decreased (P <0.01). At 8 weeks of operation, in rat ventricular remodeling in animal models with coarctation rats abdominal aorta, IVSTd, left ventricular posterior wall end-diastolic thickness(LVPWTd), left ventricular wall thickness, left ventricular cavity area, CVF, PVCA and leads of ST-segment changes increased (P <0.01), left ventricular end-diastolic diameter(LVDd) increased ( P <0.05 ) , left ventricular ejection fraction(LVEF) decreased(P <0.05), LVMI increased(P<0.01), left ventricular cavity area increased(P <0.05), heart rate increased (P <0.05), exhaustive swim time decreased (P <0.01).2. At 4 weeks of operation, in rat ventricular remodeling in animal models with coarctation rats abdominal aorta, electrophysiology index of left ventricle, including APD20,APD50 APD90 increased ( P <0.01 ) , ERP increased ( P <0.05),ERP/ APD90 decreased(P <0.05).But electrophysiology index of right ventricle have no changes. In rat ventricular remodeling in animal models with coronary artery ligation, electrophysiology index of left and right ventricle all increased.3.Electrophysiology impacts of drugs on the isolated heart of animal models with coarctation rats abdominal aorta. (1) Lidocaine : shorten the time of APD90 , increased the ratio of ERP/APD90, reduced myocardial action potential repolarization dispersion, reduced the APA, Vmax. (2) Amiodarone: extended the time of APD90 and ERP, increased the ratio of ERP/APD90, reduced myocardial action potential and effective refractory period of dispersion, extended the time of A-H and slow down the AV node conduction velocity. (3) Verapamil: extended the time of A-H. (4) GSL: extended the time of APD90, ERP (P <0.05) and A-H (P <0.01). (5) Trtramethylpyrazine (TMP): extended the time of ERP (P <0.05) and A-H (P <0.01), increased the ratio of ERP/APD90 (P <0.05). (6) GSL + TMP: extended the time of APD90 and ERP (P <0.05), increased the ratio of ERP/APD90 (P <0.05), extended the time of A-H (P <0.01). (7) Sophoridine: extended the time of APD90 and ERP (P <0.05), increased the ratio of ERP/APD90 (P <0.05), extended the time of A-H and H-V (P <0.01). (8) Berberine: extended the time of APD90 and ERP (P <0.05) increased the ratio of ERP / APD90 (P <0.05), decreased APA and Vmax (P <0.01), extended the time of A-H (P <0.01).4.Electrophysiology impacts of captopril and Fuzhenghuayufang capsule on the isolated heart of animal models with coronary artery ligation: (1) captopril: Shorten the time of APD (P <0.05), increased the ratio of ERP/APD90 (P <0.05), decreased the APD90 dispersion, induced ventricular fibrillation in aconitine dosage increased (P <0.05). (2) Fuzhenghuayufang Capsule: Shorten the time of APD (P <0.05), increased the ratio of ERP/APD90 (P <0.05), decreased the APD90 dispersion, induced ventricular fibrillation in aconitine dosage increased (P <0.05).Conclusions:1.The heart of animal models with coarctation rats abdominal aorta present typical concentric hypertrophy in early, and development combination of concentric hypertrophy and eccentric hypertrophy after sometimes. The characteristic of syndrome of traditional Chinese medicine present syndrome of Qixu and blood stasis.2. The isolated heart of two kinds of ventricles remodeling have their own electrophysiological characteristics.3. Combination gensenosides with trtram-ethylpvrazine have better electrophysiological impact on the heart of animal models with coarctation rats abdominal aorta than gensenosides or trtram-ethylpvrazine.4. Fuzhenghuayu caps and captopril, which have never been report to have antiarrhythmic function, had been found that their have some good electrophysiological impact on the animal models with coronary artery ligation.

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